Project description
Decoding sensory circuit connectivity
Disruptions in sensory processing are a hallmark of disorders like autism, schizophrenia, and bipolar disorder. These conditions often involve impaired connectivity in the brain’s sensory circuits. The thalamus, which plays a central role in processing sensory information, connects to the primary somatosensory cortex (S1) through crucial neuronal pathways. However, the precise mechanisms underlying this connectivity and its impact on sensory function remain unclear. Supported by the Marie Skłodowska-Curie Actions programme, the ThalamoLinkIT project seeks to unravel these mechanisms by focusing on the thalamic circuit’s connection to S1 neurons. By studying the role of cell surface proteins (CSPs) in synaptic formation, this research will shed light on the molecular causes of sensory processing disorders.
Objective
Sensory processing is frequently altered in disorders like autism, schizophrenia and bipolar disorder. Neuronal circuits from the thalamus to the primary somatosensory cortex (S1) play a critical role in sensory processing. Dysconnectivity of such circuits is implicated in disorders associated with sensory processing impairments. The posteromedial thalamic nucleus (POm) connects to intratelencephalic (IT) layer 5 (L5) pyramidal neurons (PNs) of S1, regulating somatosensory processing. The mechanisms regulating connectivity and function of the POm>IT L5 PN circuit remain unknown. Cell surface proteins (CSPs) drive circuit formation and specification. I hypothesize that a unique combination of CSPs orchestrate the structural and functional connectivity of this circuit, and can explain vulnerability to certain disorders. To understand the molecular mechanisms involved in POm>IT L5 PN connectivity in mice, I will first isolate POm>IT L5 PN synapses and characterize their molecular signature with mass spectrometry. Next, I will use these data and information from public databases on the genetics of neurodevelopmental disorders, to select 5 postsynaptic CSPs to further study. Using genome engineering, I will next knock-out the selected CSPs, one at a time, and analyze the impact on the structure and function of the circuit. Last, to deepen our mechanistic understanding of these proteins and gain insight to the downstream pathways, I will map changes in the molecular composition of these synapses. This project will allow us to study for the first time the molecular correlates of the functional specificity of this circuit and provide insight in the pathomechanisms of associated disorders. The experience of the de Wit lab in studying mechanisms of synapse function, the cutting-edge technologies provided by the host institute and my scientific background will enable me to push the boundaries of existing methods and achieve the highest possible quality in this project.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences computer and information sciences databases
- medical and health sciences clinical medicine psychiatry schizophrenia
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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9052 ZWIJNAARDE - GENT
Belgium
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